One of many universal requirements of implants, wherever they are used in the body, is the ability to form a suitably stable mechanical unit with neighboring hard or soft tissues. A loose (or unstable) implant may function less efficiently or cease functioning completely, or it may induce an excessive tissue response. In either case, it may cause the patient discomfort and pain. In several situations, a loose implant is deemed to have failed and has to be surgically removed.
For a long time, it has been recognized that any type of implant (whether a dental implant or orthopedic implant), should possess a biological compatibility with implant-receiving-surrounding hard and soft vital tissues. Accordingly, the material choice for implants is limited to certain types of materials, including titanium materials such as un-alloyed commercially pure titanium (ASTM Grades 1, 2, 3, 4 and 7) and Ti-based alloy such as Ti-6Al-4V, AISI Type 316L stainless steel, or some ceramic materials such as pure alumina or synthetic compounds having Ca and P ions (including hydroxyapatite or tri-calcium phosphate).
Dental or orthopedic prostheses, particularly surface zones thereof, should respond to the loading transmitting function. The placed implant and receiving tissues form a unique stress-strain field. Between them, there should be an interfacial layer. During the loading, the strain-field continuity should be held, although the stress-field is obviously in a discrete manner due to different values of modulus of elasticity of both implant material and tissues. If the magnitude of the difference in modulus of elasticity between implant and tissue is large, then the interfacial stress, accordingly, will be so large that the placed implant system will face a risky failure situation. Therefore, materials for implants or surface zone of implants should be mechanically compatible to mechanical properties of the receiving tissues, so that the interfacial stress can be minimized. This is the second compatibility and is called mechanical compatibility.
Furthermore, a third compatibility, i.e., morphological compatibility is also important. In a scientific article published by the present inventor ("Fractal Dimension Analysis Of Mandibular Bones: Toward A Morphological Compatibility Of Implants" in Bio-Medical Materials and Engineering, 1994, 4:397-407), it was found that surface morphology of successful implants has upper and lower limitations in average roughness (1.about.50 .mu.m) and average particle size (10.about.500 .mu.m), regardless of the type of implant material (metallic, ceramics, or polymeric materials). If a particle size is smaller than 10 .mu.m, the surface will be more toxic to fibroblastic cells and have an adverse influence on cells due to their physical presence independent of any chemical toxic effects. If the pore is larger than 500 .mu.m, the surface does not exhibit sufficient structural integrity because it is too coarse. This third morphological compatibility (which was proposed by the present inventor) is now well accepted in the implantology society.
The attachment of cells onto titanium surfaces is an important consideration in the areas of clinical implant dentistry. A major consideration in designing implants has been to produce surfaces that promote desirable responses in the cells and tissues contacting the implants. Cellular behaviors such as adhesion, morphologic change, functional alteration, and proliferation are greatly affected by surface properties such as hydrophilicity, roughness, charge, free energy, and morphology.
It is well known that the surface chemistry, surface energy, and surface topography govern the biological response to an implant material. The tissue response to a dental implant may involve physical factors such as size, shape, surface topography, and relative interfacial movement, as well as chemical factors associated with the composition and structure.
Biomaterials used in a living organism may come into contact with cells in the related tissue for a long period of time. For this reason, they should naturally be harmless to the organism, and the mechanical properties should be suited to the purpose, as described previously. Furthermore, they should possess biological effect capable of providing favorable circumstances for the properties and functions of the cells at the implant site. For example, materials used in the construction of an artificial heart or heart valve must provide for anti-thrombogenesis, which prevents attachment of the cellular components of blood. By contrast, materials for a dental or bone implant must be suitable for cell attachment, because both the connective and epithelial cells (with which these materials mainly come into contact) are anchorage-dependent and therefore need a cell attachment scaffold for cell division and cell differentiation to be conducted. Therefore, "attachability" of the cells to the material is one of the important parameters in the evaluation of biomaterials.
Surface properties of biomaterials play a critical role in the adhesion process of adjacent cells. Little is known about the optimal surface characteristics of titanium that promote tissue-implant interaction. Cell adhesion to and spreading on a biomaterial are, amongst other factors, dependent on the surface wettability of the biomaterial. Measurement of the wettability of a material, expressed by the contact angle in the presence of the different liquids, might be a predictive index of cytocompatibility. Surface modification of titanium surfaces has been shown to improve bony apposition, tissue adhesion, and migration. With the surface chemistry of titanium altered, different rates of cellular attachment have been observed. However little is known about the biochemical responses of cells to other surface properties, such as oxide thickness, oxide crystal structure, surface topography, or the dynamic surface changes which can occur after implantation.
It has been shown that methods of implant surface preparation can significantly affect the resultant properties of the surface and subsequently the biological responses that occur at the surface. Recent efforts have shown that the success or failure of dental implants can be related not only to the chemical properties of the implant surface but also to the micromorphologic nature of the surface.
Many clinical studies on dental implants have focused on the success of endosseous implants with a variety of surface characteristics. In an attempt to improve the quantity and quality of the bone-implant interface, numerous implant surface modifications have been proposed.
In order to achieve morphological compatibility, titanium implant surfaces need to be modified. They can be treated by additive methods such as the titanium plasma spray procedure to increase surface area. They have also been modified by subtractive methods such as acid pickling, acid etching, sandblasting and other small particle-blasting to change the texture as well as to increase the effective surface area. The development and use of these surface modifications have been based on the theory that improved osseointegration can be achieved by increasing the topography or roughness of the implant surface.
As briefly mentioned above, to modify the surface layer, there are mainly two types of textures, i.e., (1) convex texture and (2) concave texture. Additive treatments such as plasma spray coating or depositing of hydroxyapatite particles or titanium beads are preformed to create convex surface morphology. There are some possibilities with the surface convex treatments to loosen or detach the deposited particles. In contrast, mechanical treatments such as sandblasting or chemical treatment can create concave surface texture.
Reviewing previous works, there are several relevant articles published. Micheals at el. ("In vitro Cell Attachment Of Osteoblast-like Cells To Titanium", J. Dent. Res., 1989, 68:276) determined that a higher percentage of osteoblast-like cells attached to rough commercially pure titanium (CPT) surfaces produced by sandblasting than to smoother surfaces which were polished with 1 .mu.m diamond paste. It was suggested that it is possible to control short-term in vitro cellular attachment and morphology by altering surface micromorphology.
Thomas et al. ("The Effects Of Surface Macrotexture And Hydroxyapatite Coating On The Mechanical Strengths And Histologic Profiles Of Titanium Implant Materials", J. Biomed, Mater, Res., 1987, 21:1395-1414) found that roughened surfaces have an increased implant surface area that results in greater surface coverage by bone as compared to smooth-polished surfaces.
Buser et al. ("Influence Of Surface Characteristics On Bone Integration Of Titanium Implants. A Histomorphometric Study In Miniature Pigs", J. Biomed. Mater. Res., 1991, 25:889-902) reported that increased surface area positively correlated with an increased bone-implant contact. It was also reported that the highest extent of bone-implant interface was observed in sandblasted and acid attacked surfaces (HC1/H.sub.2 SO.sub.4) and hydroxyapatite-coated implants.
Several investigators have demonstrated that implant surface roughness enhances the osseointegration of implants to bone as determined by torque removal tests. Torque removal forces have been used as a biomechanical measure of anchorage or osseointegration in which the greater forces required to remove implants may be interpreted as an increase in the strength of osseointegration. Wilke et al. ("The Influence Of Various Titanium Surfaces On The Interface Shear Strength Between Implants And Bone", Clinical Implant Materials Advances In Biomaterials Amsterdam: Elsevier, 1990, 9:309-314) found, when comparing six groups of different surface structures, that the highest required removal torque was needed for the acid treated screws with a rough surface. Screw shaped implants with surfaces that were sandblasted and acid etched (HCl/H.sub.2 SO.sub.4) achieved higher resistance to reverse torque rotation than screw shaped implants with surfaces that were either electropolished, sandblasted and acid pickled (HF/HNO.sub.3) or titanium plasma-spray coated.
Klokkevold et al. ("Osseointegration Enhanced By Chemical Etching Of The Titanium Surface. A Torque Removal Study In The Rabbit", Clin. Oral Implants Res., 1997, 8:442-227) compared torque resistance to removal of screw shaped titanium implants having an acid etched (HCl/H.sub.2 SO.sub.4) surface with implants having a machined surface which is relatively smooth. Resistance to torque removal was found to be four times greater for the implants with the acid etched surface as compared to the implants with the machined surface. It was suggested that chemical etching of the titanium implant surface significantly increased the strength of osseointegration as determined by resistance to reverse torque rotation.
Cochran et al. ("Bone Response To Unloaded And Loaded Titanium Implants With A Sandblasted And Acid-etched Surface: A Histometric Study In The Canine Mandible", J. Biomed. Mater. Res., 1998, 40:1-11) found that a sandblasted and acid-etched titanium implant had a greater bone-to-implant contact than did a comparably-shaped implant with a titanium plasma sprayed surface.
In an in vitro study, Bowers at al. ("Optimization Of Surface Micromorphology For Enhanced Osteoblast Responses in vive", Int. J. Oral Maxxiofac, Implants, 1992, 7:302-310) found significantly higher levels of attachment of osteoblast-like cells to a rough sandblasted surface with irregular morphology when compared to smooth and regular surfaces.
The above showings of beneficial effect of mechanical and chemical roughening titanium surfaces confirm the desirability of morphological compatibility, which the present inventor has proposed and is now well accepted.
Another approach was recently developed to improve bone-titanium bonding. Kokubo et al. ("Spontaneous Apatite Formation On Chemically Surface Treated Ti", J. Amer. Ceram. Soc., 1996, 79:1127-1129) showed that, after a combination of alkali and heat treatment, bone-like apatite forms on the surface of titanium in a simulated body fluid, that has an ion concentration nearly equal to that of human blood plasma. Apatite formation on the material surface is believed to be a prerequisite for bioactivity, that is, direct bone bonding.
In an animal study, Yan et al. ("Bonding Of Chemically Treated Titanium Implants To Bone", J. Biomed. Mater. Res., 1997, 37:267-275) reported that alkali-treated (in 4M NaOH at 60.degree. C. for 24 hours) and heat-treated (in air oxidation at 600.degree. C. for 1 hour) titanium can bond to bone directly. Also shown was that titanium (that is soaked in a simulated body fluid after alkali and heat treatments) has bone-bonding ability. It was found that a Ca-P rich layer was detectable at the interface between bone and alkali- and heat-treated titanium implants and enhanced the strength of bone-implant bonding by inducing a bioactive surface layer on titanium implants.
Kim et al., ("Preparation Of Bioactive Ti And Its Alloys Via Simple Chemical Surface Treatment", J. Biomed. Mater. Res., 1996, 32:409-417) reported that after alkali (10M NaOH or 10M KOH at 60.degree. C. for 1 to 24 hours) and heat treatments (in air oxidation at 400.degree. C. to 800.degree. C.), a bone-like apatite layer also formed on the surface of titanium alloys such as Ti-6Al-4V, Ti-6Al-2Nb-Ta, and Ti-15Mo-5Zr-3Al in a simulated body fluid. As with alkali- and heat-treated pure titanium, these alloys are thought to be able to bond directly via alkali and heat treatments.
During wet oxidation in either boiling acid or anodization, a concave surface is normally produced due to the selective dissolution and subsequent oxidation. This is chemical modification. The concave texture can also be created mechanically. It is generally believed that the roughness of as-blasted or as-peened surface is about 1/5 to 1/10 of the size of used media (Y.Oshida et al., "Effects Of Shot-penning On Surface Contact Angles Of Biomaterials", J. Mater. Sci.: Mater. in Medicine,. 1993, 4:443-447). This is a mechanical modification. If the multi-mold concave texture is desired, the mechanical texturing and chemical treatments can be combined. This is then mechano-chemical modification, or chemi-mechanical modification. Furthermore, during the above treatment, surface of titanium materials will be covered with oxide film with appropriate thickness. The crystalline structure of these oxide films will be varied, depending on the chemistry used. Moreover, the crystalline structure of titanium oxide film can also be controlled and altered by thermal treatments such as oxidation. This is thermal modification. Hence, some treatments could involve mechano-chemical thermal modification.
Certain information is already known about the crystalline structure of titanium oxides. Titanium is a very active element. When fresh titanium is exposed to the atmosphere by such cutting acts as lathing, milling, or sawing, an oxide layer begins to form within nanoseconds. After only one second, a surface oxide with some 20 to 50 .mu.m in thickness will form. The characteristic composition and structure of the oxide layer often differ depending on the technique used to prepare the surface of the metal. The exact composition of the oxide, TiO.sub.x, (where x is a number in the range from 1.0 to 2.0), its morphology and content of low concentrations of impurity elements, are examples of properties that may be varied in a controlled manner.
There are seven possible types of oxide, TiO.sub.x, formed on titanium materials. They include (1) amorphous oxide, (2) cubic TiO (a.sub.o =4.24 .ANG.), (3) hexagonal Ti.sub.2 O.sub.3 (a.sub.o =5.37 .ANG., .alpha.=56.degree.48'), (4) tetragonal TiO.sub.2 (anatase) (a.sub.o =3.78 .ANG., c.sub.o =9.50 .ANG.), (5) tetragonal TiO.sub.2 (rutile) (a.sub.o =4.58 .ANG., c.sub.o =2.98 .ANG.), (6) orthorhomic TiO.sub.2 (brookite) (a.sub.o =9.17 .ANG., b.sub.o =5.43 .ANG., c.sub.o =5.13 .ANG.), and (7) non-stoichiometric oxide.
It was found that amorphous titanium oxide film which was formed during chromic acid anodization, was converted to a crystalline rutile by heating the amorphous film in distilled water at 85.degree. C. for 100 hours. The transformation of amorphous titanium dioxide to anatase to further rutile was consistent and the rate of the transformation is accelerated by increasing temperature and decreasing solution pH. (A. Matthews "The Crystallization Of Anatase And Rutile From Amorphous Titanium Dioxide Under Hydro Thermal Conditions", Amer. Miner, 1976, 61:419-424).
Crystallinity, which is judged by the sharpness of diffraction lines, decreased according to the treatment in the following order (K. W. Allen et al., "Titanium And Alloy Surfaces For Adhesive Bonding", A Adhesion, 1974, 6:229-237): (higher degree) alkaline hydrogen peroxide.fwdarw.phosphate fluoride.fwdarw.hydrofluoric acid.fwdarw.anodic oxidation.fwdarw.hydrochloric acid.fwdarw.sulphuric acid (lower degree).
Much work has been done to identify the crystallography of titanium oxides formed with various acids
. A mixture of anatase and rutile was identified under a wet oxidation using boiling 0.1 weight % H.sub.2 SO.sub.4 for 24 hours, while a mixture of anatase and brookite was obtained in the boiling 0.2 weight % HCl oxidation for 24 hours (T. Koizumi et al., "Structure Of Oxide Films Formed On Ti In Boiling Dilute H.sub.2 SO.sub.4 and HC1", Corrosion Sci., 1968, 8:195-196). Only anatase phase was identified under anodization using 0.1 M H.sub.2 SO.sub.4 at 30.degree. C. at 12.5 mA/cm.sup.2 (J.Yhalom et al., "Electrolytic Breakdown Crystallization Of Anodic Oxide Films on Al, Ta and Ti", Electrochimica Acta, 1970, 15:1429-1435), or 0.1 M H.sub.2 SO.sub.4 at 5 V (T. Ohtsuka, "Structure Of Anodic Oxide Films On Titanium" Surface Sci., 1998, 12:799-804). On the other hand, solely rutile structure was obtained by wet oxidation using boiling 10 weight % HCl (A.Felske et al., "Raman Spectroscopy Of Titanium Dioxide Layers", Electrochimica Acta, 1989, 34:75-77), boiling 10 weight % H.sub.2 SO.sub.4 (E. P. Lautenschlager et al., "Titanium And Titanium Alloys Such As Dental Materials", Int. Dent. J., 1993, 43:245-253), or anodization using 0.5 M H.sub.2 SO.sub.4 at 5 to 10 V (K. W. Allen et al., ibid). It was found that neutral, alkaline, and mildly acidic conditions favor anatase formation, whereas more strongly acid environments favor rutile formation (A. Matthews, ibid).
As mentioned above, measurements of the wettability of a material surface, expressed by the contact angle in the presence of different liquids, might be a predictive index of cytocompatibility and cell attachability.
Surface wettability is largely dependent on surface energy and influences the degree of contact with the physiological environment, as described above. Increased wettability (or decreased contact angle) enhances interaction between the implant surface and the biological environment.
Wettability on the surfaces of biomaterials is reported to affect cell attachment considerably. The reason is believed to be that microvilla and filopodia, which work advantageously at the early stage of the cell attachment, are needed for the cells to pass through the energy barrier between the material and the cells themselves. Hence, cell attachment in its early stage is affected by physical and chemical properties, including the wettability. It has been pointed out that cell attachment to the material is closely related to wettability of its surface. It is, for this reason, that the focus of biomaterials development has shifted to the control of wettability of the material surface and attachment of tissue to the implant site. Previous research reports on the wettability of materials and their effects on tissue, but failed to define the wettability clearly and did not clarify the effect caused by surface configuration and crystalline structure of surface oxides.
According to Yanagisawa et al., ("Effects Of "Wettability" Of Biomaterials On Culture Cells", J. Oral Implantol., 1989, 15:168-177), it was found that the contact angles (.theta.) of materials affected both the cell attachment and spreading rates (d.theta./dt). With small contact angles and high wettability, the cell attachment rate was high, while it was low when the contact angles were large and wettability was low. Thus, they concluded that wettability of biomaterials is considered to be an important parameter of biological effect at the cell level.
The media used for the contact angle measurement must meet several requirements: (1) not be highly viscous, (2) not be of high specific weight, and (3) not be chemically active against the substrate surface. It appears to be that distilled (or deionized) water is normally employed. Glycerol and 1% NaCl solution have also been used. The different types of liquids (water, diiodomethane, glycerol, ethylene glycol) showed different degrees of contact angles. However, it was reported that these differences were not consistent among the different surface preparations (Yanagisawa et al., ibid.).
Few investigations have related the influence of surface roughness and crystalline structure on wettability and spreadability (for example, Y.Oshida et al., "Effects Of Shot-peening On Surface Contact Angles Of Biomaterials", J. Mater. Sci.: Mater, in Medicine, 1993, 5:443-447). Shot peening is an advanced technique to create controlled surface topographic features along with other engineering benefits, including generating surface compressive residual stress. It was suggested that the wettability and spreadability appear to be related to the crystalline structure of the oxide films formed on these biomaterials. It was, therefore, suggested that the surface energy (monitored from the contact angle measurement) relates to the crystalline structure of surface oxide films. It was also observed, for shop peening and pre-oxidized surfaces, that changes in contact angles as a function of time are strongly dependent upon the type of surface oxide. A higher spreading rate is observed on biomaterials whose surfaces are covered with TiO.sub.2 while a lower spreading coefficient is seen on cubic structure oxides including spinel type oxide formed on stainless steel.